This comprehensive five-year career development plan has a two-fold purpose: 1) to bring about the candidate's development into an independent clinical investigator through a combination of formal didactic coursework, directed mentoring and the conduct of the research project detailed within this application, 2) to render knowledge of the association between blood pressure variability (BPV) and cardiovascular (CV) disease in patients treated with hemodialysis (HD). Identification of novel and potentially reversible CV risk factors in HD patients is of paramount importance given the exceedingly high CV mortality rate in this population. Data in animal models and in non-uremic patients suggest that a potentially causal assocaiton between BPV and CV disease exists. Given both the dramatic CV burden and volatile nature of blood pressure in patients treated with HD, study of this association is compelling. The long-term goals of this line of research are: to determine if a causal association between BPV and CV disease exists in HD patients, and to develop targeted interventions aimed at reducing CV morbidity and mortality in HD patients via reductions in BPV. This line of research will serve as an ideal platform for the candidate's development into an independent investigator. The specific aims of this study are: 1) to describe the distribution of blood pressure variability in a representative sample of Philadelphia HD patients, 2) to define clinical factors that predict BPV and 3) to determine whether a causal association exists between blood pressure variability and cardiovascular mortality and hospitalization for CV disease. Given that randomization to various levels of BPV is neither possible nor ethical, a prospective cohort design was chosen. PUBLIC HEALTH RELEVANCE: Patients undergoing dialysis die from cardiovascular disease at very high rates, making identification of risk factors in this population critically important. This study is designed to examine whether one potential risk factor, variability in blood pressure over time, causes or contributes to cardiovascular disease in dialysis patients.